Iron sparing and recycling in a compartmentalized cell

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Highlights

  • Increased iron uptake is not the only mechanism to combat poor iron supply.

  • Iron sparing, recycling and prioritizing proteins for iron loading are key.

  • Chlamydomonas provides an opportunity to explore subcellular iron distribution.

This review focuses on economizing, prioritizing and recycling iron in Chlamydomonas, a reference organism for discovering mechanisms of acclimation to poor iron nutrition in the plant lineage. The metabolic flexibility of Chlamydomonas offers a unique opportunity to distinguish the impact of iron nutrition on photosynthetic versus respiratory metabolism, and the contribution of subcellular compartments to iron storage and mobilization. Mechanisms of iron sparing include down regulation of protein abundance by transcript reduction or protein degradation. Two well-studied examples of hierarchical iron allocation are the maintenance of FeSOD in the plastid and heterotrophic metabolism in acetate-grown cells at the expense of photosynthetic metabolism. The latter implicates the existence of a pathway for inter-compartment iron recycling when access to iron becomes limiting.

Introduction

Photosynthetic organisms have a relatively high iron quota. As in other eukaryotes, all four electron transfer complexes plus cytochrome c in the mitochondrial respiratory chain require iron-sulfur clusters and/or hemes as redox cofactors in electron transfer (Figure 1a). Uniquely, an additional demand on iron assimilation is created by the photosynthetic electron transfer chain (ETC), where all proteins catalyzing so-called ‘linear’ electron transfer from water to ferredoxin require iron to function (Figure 1b). The one exception is in the transfer of an electron between cytochrome b6f and photosystem I, which is often catalyzed by the copper-containing protein plastocyanin. However, some microbes use a heme-containing protein, cytochrome (Cyt) c6, either constitutively or conditionally in a situation of poor copper nutrition to replace plastocyanin.

Respiration requires more iron per unit (Figure 1), but the chloroplast is the major sink for iron in the cell. Roughly 80% of the cellular iron found in green leaves is located in the chloroplasts [1, 2], indicating the importance in the plant lineage of the chloroplast as a site of iron utilization. Likewise, in the single-celled alga Chlamydomonas reinhardtii, the mitochondria occupy less than one-tenth of the cell volume compared to the single, cup-shaped chloroplast [3, 4], again making the chloroplast the dominant iron sink.

The iron-dependent bioenergetic complexes in both the photosynthetic and respiratory ETCs are assembled in the chloroplast or mitochondrion, respectively. In the absence of an iron source (iron-chelate or heme), the complexes fail to accumulate, generally because of thermodynamic instability and protease susceptibility of individual apoproteins. It is evident that when iron availability is insufficient to maintain the cellular iron quota for a particular growth condition, there is likely to be competition between the chloroplast and the mitochondrion for this redox cofactor. How is iron delivery and utilization prioritized to one organelle over another? Within the organelle, how is the hierarchy of iron delivery/distribution to individual apoproteins maintained, and how does it change as a function of metabolism?

When the environmental supply cannot meet the cellular demand, prevailing dogma is that mechanisms for economizing, prioritizing and recycling the limiting metal nutrient are initiated [5]. This is driven by maintenance of more essential biochemical functions over dispensable ones where possible and by priming macromolecular metabolism so that upon metal resupply, proteins in key pathways are prioritized for cofactor loading. This review focuses on the extent to which these mechanisms are known to exist as part of the nutritional iron homeostasis pathway in C. reinhardtii (Figure 2).

Section snippets

Chlamydomonas

C. reinhardtii (referred to as Chlamydomonas) provides a unique opportunity to explore the cellular and subcellular dynamics of metal acquisition, trafficking and allocation in the plant lineage. Several paradigms in trace metal homeostasis have been established with the use of Chlamydomonas as a reference organism, including the use of ‘back-up’ enzymes for metal-sparing and, more recently, the concept of ‘hot bunking’ [10] or metal cofactor-recycling from one pathway to another [11, 12••].

Iron sparing

A ubiquitous method for acclimating to poor iron nutrition is iron sparing. Potential iron-binding proteins are not synthesized, synthesized at a much lower rate, or degraded before they can compete for the precious nutrient. Iron that is brought into the cell or mobilized from cellular stores can be prioritized for less dispensable iron-dependent functions, such as DNA repair/synthesis [18].

Most examples of iron sparing have come from studies with bacteria and yeast, and post-transcriptional

Degradation of proteins with bound iron

Another mechanism to economize on iron may involve degradation of proteins that bind iron. However, it should be noted that in most cases a distinction has not been made between iron-deficiency induced proteolysis and normal degradation coupled to unsuccessful de novo synthesis due to the absence of transcript or cofactor.

Two types of iron homeostasis studies are routinely performed with Chlamydomonas: iron nutrition and iron starvation. In iron nutrition studies, Chlamydomonas cultures are

Preferential maintenance of indispensable iron-dependent proteins

The down-regulation of gene expression, the activation of transcript degradation and initiation of proteolysis serve to spare iron. Concurrently, a second group of iron-dependent proteins are maintained and appear to be prioritized for iron acquisition. In response to poor iron supply, this might involve increased gene expression to provide more transcripts for increased synthesis (Supplementary Table 1), increased translation of a prioritized protein, or alternatively, by a mechanism that

The impact of metabolism on iron status and vice versa

The metabolic state of the cell can have a large impact on the need for iron-dependent proteins. For instance, with regards to nitrogen metabolism, nitrogen-fixation requires more iron than does nitrate assimilation, which in turn requires more iron than ammonium assimilation [33]. Consequently, the cell responds to the nitrogen source by adjusting iron uptake. Several examples are available from iron-use studies with marine cyanobacteria and diatoms. Siderophore (iron chelator involved in iron

Cofactor recycling

Compared to iron-economizing strategies, which are readily evident, it is more difficult to document iron recycling. The fact that it occurs is implied in two recent works. The first example is degradation of the iron-rich photosynthetic apparatus at night concomitant with the synthesis of the iron-rich nitrogenase enzyme in C. watsonii [10], which allows the cyanobacterium to survive on a permanently reduced Fe quota. The second example is the re-synthesis of Fe-SOD subsequent to the loss of

Conclusions

Although iron is a relatively abundant element in the earth's crust, many organisms are transiently or chronically limited by access to this nutrient. In neutral to alkaline soil, iron is predominately found in poorly soluble complexes, such as ferric oxides. These complexes create a major obstacle for photosynthetic eukaryotes, which have many of the same iron demands as non-photosynthetic eukaryotes but with the added burden of supplying a relatively substantial amount of iron to the

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgments

This work was supported by the Division of Chemical Sciences, Geosciences, and Biosciences, Office of Basic Energy Sciences of the U.S. Department of Energy (DE-FD02-04ER15529).

C.E.B.-H. acknowledges support from an Individual Kirschstein National Research Service Award from the National Institutes of Health (GM100753).

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